Local circuit inhibition is emerging as one of the primary mechanisms controlling neuroendocrine secretion. The electrical activity of hypothalamic magnocellular neuroendocrine cells (MNCs), which produce the peptide hormones oxytocin and vasopressin, is known to determine directly the amount of hormone released in the blood circulation. GABA-mediated synaptic potentials are known to have a profound influence on membrane conductance in central mammalian neurons. The goal of this research is to determine how local inhibitory neurons regulate identified neuroendocrine cells in the supraoptic nucleus (SON) using the rat hypothalamic slice preparation. We will microapply glutamate to selectively stimulate the soma-dendritic regions of local GABAergic neurons located at the periphery of he supraoptic nucleus. Spontaneous and glutamate-evoked inhibitory postsynaptic currents (IPSCs) will be recorded with the whole-cell patch-clamp pipette will be combined with immunohistochemical identification of the peptidergic content of the recorded cell. Our specific goals are to determine 1) whether local GABAergic neurons located near the periphery of the SON provide inhibitory input to vasopressinergic and/or oxytocinergic MNCs, 2) whether each MNC receives input from several GABAergic neurons (i.e., convergence), 3) whether each inhibitory neuron projects to several MNs (i.e., divergence), and 4) whether individual inhibitory neurons contact only one type of MNC (i.e., each GABAergic neuron inhibits either vasopressinergic or oxytocinergic MNCs, but not both types of cells). The proposed studies will provide fundamental information on the functional importance that local inhibitory circuits have in the magnocellular neuroendocrine system, the classical model for hypothalamic-pituitary neurosecretion in mammals.